Alcohol is classified pharmacologically as a central nervous system depressant. The cellular mechanisms that underlie this alcohol-induced depression of nervous system excitability, however, are poorly understood. This project investigated excitability mechanisms in neuronal precursor cells. Precursor cells from the anterior subventricular zone (SVZa) of neonatal rat forebrain express neuron-specific markers and divide while migrating along the path to the olfactory bulb, where they differentiate into granule and periglomerular interneurons. SVZa cells also express neuron specific tubulin and divide in vitro. Voltage-dependent membrane ion channels have been studied in SVZa cells after 1 day in culture (J Neurophysiol 1999; 81:95). In this study, the responses of both voltage-dependent channels and neurotransmitter receptors were determined for SVZa cells in both culture and slices. Whether in culture or in slice, SVZa cells displayed voltage-dependent sodium and potassium currents, were sensitive to the neurotransmitter GABA (1-300 uM), but were insensitive to 100 uM NMDA, 100 uM kainate, 24 uM glutamate, 100 uM ATP or 100 uM acetylcholine. Thus, many of the properties of SVZa cells observed after 1 day in culture are observed in SVZa cells in slice. Although GABA inhibits neurons in the adult CNS, during development GABA depolarizes SVZa cells and newly differentiating neurons. In addition, GABA has been shown to regulate cell proliferation and migration, as well as to act as a trophic factor in other types of cells. In the future, we plan to examine the role of GABA in the migration and differentiation of SVZa cells, and the effect of ethanol on GABA responses in these cells.